ABSTRACT
TGF-ß affects virtually all aspects of mammalian physiology starting from early embryonic development to adult
tissue homeostasis through regulation of diverse cellular functions including proliferation, differentiation, and
apoptosis. TGF-ß signaling also plays an important role in cell metabolism, although there has been incremental
progress in understanding how it differentially regulates mitochondrial biogenesis, respiration, and organelle
destruction. While such varying effects are theorized to occur primarily through slow-acting contextual gene
regulation, TGF-ß is also capable of inducing more rapid, direct, and reversible changes in mitochondrial shape
and function through largely unknown mechanisms- a key aspect that represents an important knowledge gap
in the field. Our research program has focused on two powerfully opposing mechanisms by which two major
TGF-ß effectors, Smad2 and TAK1, control mitochondrial fusion/fission dynamics to achieve and maintain
metabolic homeostasis. We seek to understand mechanisms governing their organization, activation, and
regulation in mitochondrial remodeling and how they influence cell behavior using angiogenesis as a
developmental model system. Our studies will provide unique perspectives on how the complex TGF-ß signaling
networks control mitochondrial dynamics to affect their metabolic, developmental and homeostatic roles in
vascular physiology.